2. Academic Validation
  3. Chalcone derivatives from licorice inhibit human and rat gonadal 3β-hydroxysteroid dehydrogenases as therapeutic uses

Chalcone derivatives from licorice inhibit human and rat gonadal 3β-hydroxysteroid dehydrogenases as therapeutic uses

  • J Ethnopharmacol. 2023 May 26;116690. doi: 10.1016/j.jep.2023.116690.
Lei Ye 1,  Ming Su 2,  Xinyi Qiao 3,  Shaowei Wang 4,  Ke Zheng 3,  Yang Zhu 5,  Huitao Li 5,  Yiyan Wang 6,  Ren-Shan Ge 7
Affiliations

Affiliations

  • 1 Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, 325000, Zhejiang Province, China.
  • 2 Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, 325000, Zhejiang Province, China.
  • 3 Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
  • 4 Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
  • 5 Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
  • 6 Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address: [email protected].
  • 7 Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, 325000, Zhejiang Province, China. Electronic address: [email protected].
PMID: 37245711 DOI: 10.1016/j.jep.2023.116690
Abstract

Ethnopharmacological relevance: In traditional Chinese medicine, licorice (the roots of Glycyrrhiza glabra and G. inflata) has been used to treat inflammation and sexual debility for over 1000 years. Pharmacological studies have identified many biologically active chalcone derivatives from licorice.

Aim of the study: Human 3β-Hydroxysteroid dehydrogenase 2 (h3β-HSD2) catalyzes the formation of precursors for sex Hormones and corticosteroids, which play critical roles in reproduction and metabolism. We explored inhibition and mode action of Chalcones of inhibiting h3β-HSD2 and compared it with rat 3β-HSD1.

Materials and methods: We investigated the inhibition of 5 Chalcones on h3β-HSD2 and compared species-dependent difference with 3β-HSD1.

Results: The inhibitory strength on h3β-HSD2 was isoliquiritigenin (IC50, 0.391 μM) > licochalcone A (0.494 μM) > licochalcone B (1.485 μM) > echinatin (1.746 μM) >chalcone (100.3 μM). The inhibitory strength on r3β-HSD1 was isoliquiritigenin (IC50, 0.829 μM) > licochalcone A (1.165 μM) > licochalcone B (1.867 μM) > echinatin (2.593 μM) > chalcone (101.9 μM). Docking showed that all chemicals bind steroid and/or NAD+-binding site with the mixed mode. Structure-activity relationship analysis showed that strength was correlated with chemical's hydrogen bond acceptor.

Conclusion: Some Chalcones are potent h3β-HSD2 and r3β-HSD1 inhibitors, possibly being potential drugs to treat Cushing's syndrome or polycystic ovarian syndrome.

Keywords

3β-HSD; Chalcone; Isoliquiritigenin; Licochalcone; Structure-activity relationship.

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